Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Toripalimab · 3 trials · 12 indications
Proportion of patients who have not experienced disease recurrence/progression or death from any cause at 1 year from start of treatment. Radiologic (CT or MRI) imaging as well as direct visualization by laryngoscopy will be used to assess disease with recurrence requiring a biopsy to be considered positive.
Time between the date of registration and the first date of documented recurrence, regardless of discontinuation of study drug, or death due to any cause, assessed at 3 years
pTRR is defined as the proportion of participants that experience a complete pathologic response or partial pathologic response during treatment, as defined in the RECIST criteria.
| Arm | Type | Description |
|---|---|---|
| toripalimab + carboplatin + paclitaxel | EXPERIMENTAL | Prior to treatment: Assessments include laryngoscopy and anatomic imaging studies Treatment: toripalimab 240mg IV with carboplatin (AUC 5) and paclitaxel (175 mg/m\^2) IV every 3 weeks for two cycles. (Cisplatin 75mg/m\^2 can be used in place of carboplatin at the investigator's discretion.) After 2 Cycles of Treatment: Repeat laryngoscopy and anatomic imaging studies. Undergo swallowing function and extranodal extension status assessment. |
| Post-bioselection: Chemoradiation + toripalimab monotherapy | EXPERIMENTAL | Patients with PR ≥50% (not CR) with preserved swallowing function or CR, with preoperative N+ disease and extranodal extension upon neck dissection. Induction Treatment: toripalimab 240mg IV+carboplatin (AUC 5)+paclitaxel (175 mg/m\^2) IV Q Continuation Treatment: toripalimab 240mg IV + carboplatin (AUC 5) + paclitaxel (175 mg/m\^2) IV Q + Radiation therapy as per the Intervention Description + toripalimab 240mg IV monotherapy for 8 cycles |
| Post-bioselection: Radiation + toripalimab monotherapy | EXPERIMENTAL | Patients with CR, with preoperative N0 disease or N+ disease with no extranodal extension upon neck dissection. Induction Treatment: toripalimab 240mg IV+carboplatin (AUC 5)+paclitaxel (175 mg/m\^2) IV Q Continuation Treatment: Radiation therapy as per the Intervention Description + toripalimab 240mg IV monotherapy for 8 cycles |
| Treatment (toripalimab) | EXPERIMENTAL | Eligible consenting participants receive toripalimab intravenously every 3 weeks for 6 months (8 doses) in the absence of disease recurrence or unacceptable toxicity. Following this, patients undergo surveillance follow up with blood tests, computed tomography (CT) scans, colonoscopy at specified intervals until 5 years post-resection. For patients who have a recurrence, a biopsy will be performed at the time of recurrence. |
| Arm 1: Toripalimab and Docetaxel Plus Carboplatin (TCD) | EXPERIMENTAL | * Baseline visit with imaging * Cycles 1 and 2 (21 day cycles) * Day 1: Predetermined dose of Toripalimab 1x daily * Day 1: Chemotherapy: predetermined dose of Docetaxel 1x daily and Carboplatin 1x daily * Tumor assessment by imaging * Surgical resection of tumor |
| Arm 2: Post Operative Radiation Therapy + Toripalimab | EXPERIMENTAL | After pathology assessment, participants with a pathological treatment response of 2 will be assigned radiation therapy per standard practice guidelines and predetermined dose of Toripalimab 1x every 3 weeks for up to 8 cycles (21 day cycles). -Follow up: every 3 months for 1 year. Imaging at 3 months |
| Arm 3: Post Operative Radiation Therapy With or Without Chemotherapy | EXPERIMENTAL | After pathology assessment, participants with a pathological treatment response of 2 or less will be assigned standard radiation therapy with or without standard of care Cisplatin-based chemotherapy as recommended per treatment team and standard practice guidelines. -Follow up: every 3 months for 1 year. Imaging at 3 months |
| Name | Type | Description |
|---|---|---|
| Toripalimab | DRUG | A monoclonal antibody (recombinant humanized programmed cell death protein 1 (PD-1) monoclonal antibody that acts as a checkpoint inhibitor) used for the treatment of melanoma and nasopharyngeal carcinoma. |
| Carboplatin | DRUG | A chemotherapy medication classified as an alkylating agent. It contains the metal platinum, which binds to DNA in cancer cells, preventing their replication and leading to cell death. This mechanism makes it effective against rapidly dividing cells, such as cancer cells. |
| Cisplatin | DRUG | \*Can be used in place of carboplatin at the investigator's discretion. A chemotherapy medication classified as an alkylating agent. It contains the metal platinum, which binds to DNA in cancer cells, preventing their replication and leading to cell death. This mechanism makes it effective against rapidly dividing cells, such as cancer cells. |
| Paclitaxel | DRUG | A chemotherapy drug that works by slowing or stopping cancer cell growth. |
| Radiation Therapy | RADIATION | Megavoltage energy photon beam irradiation. Any treatment planning and delivery system that has been credentialed for head and neck intensity-modulated radiotherapy (IMRT). Simultaneous integrated boost and sequential boost techniques (discretion of treating physician). Total doses delivered to each Planning Target Volume (PTV) (in 33-35 fractions): High: 70 Gy, Boost (if applicable): 66 Gy, Intermediate: 60-63 Gy, Elective: 56-57 Gy A sequential boost will consist of treatment of the combined PTVs 25 fractions followed by three sequential cone-downs targeting (Intermediate + Boost + High); (Boost + High); and High. Total doses for the PTVs: High: 70 Gy, Boost (if applicable): 66 Gy, Intermediate: 60 Gy, Elective: 50 Gy. |
| Biopsy Procedure | PROCEDURE | Undergo biopsy |
| Biospecimen Collection | PROCEDURE | Undergo collection of blood samples |
| Colonoscopy | PROCEDURE | Undergo colonoscopy |
| Computed Tomography | PROCEDURE | Undergo CT |
| Questionnaire Administration | OTHER | Ancillary studies |
| Docetaxel | DRUG | A taxoid antineoplastic agent, single-dose vials, via intravenous (into the vein) infusion per standard of care. |
Inclusion Criteria: 1. Pathologically confirmed and previously untreated squamous cell carcinoma of the larynx or hypopharynx 2. AJCC 8th Edition Stage III - IV disease (T1-T2/N1-N3, T3-T4/N0-N3) 3. Disease (primary \& nodal) must be potentially surgically resectable and curable with conventional s...